JPH02184659A - Preparation of trans-1,1,2-triphenyl-buto-1-ene derivative - Google Patents
Preparation of trans-1,1,2-triphenyl-buto-1-ene derivativeInfo
- Publication number
- JPH02184659A JPH02184659A JP63332691A JP33269188A JPH02184659A JP H02184659 A JPH02184659 A JP H02184659A JP 63332691 A JP63332691 A JP 63332691A JP 33269188 A JP33269188 A JP 33269188A JP H02184659 A JPH02184659 A JP H02184659A
- Authority
- JP
- Japan
- Prior art keywords
- trans
- hydrochloric acid
- sulfuric acid
- cis
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 22
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000003960 organic solvent Substances 0.000 claims abstract description 9
- 239000007795 chemical reaction product Substances 0.000 claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims 2
- 238000010438 heat treatment Methods 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 10
- 239000000203 mixture Substances 0.000 abstract description 8
- 238000000034 method Methods 0.000 abstract description 7
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 abstract description 5
- 238000004587 chromatography analysis Methods 0.000 abstract description 4
- 230000018044 dehydration Effects 0.000 abstract description 3
- 238000006297 dehydration reaction Methods 0.000 abstract description 3
- 239000012452 mother liquor Substances 0.000 abstract description 3
- 238000006243 chemical reaction Methods 0.000 abstract description 2
- 238000002425 crystallisation Methods 0.000 abstract description 2
- 230000008025 crystallization Effects 0.000 abstract description 2
- 238000002955 isolation Methods 0.000 abstract description 2
- 238000000926 separation method Methods 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 230000001833 anti-estrogenic effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- HFHRSBKYURPWRU-UHFFFAOYSA-N 1,1-diphenylbut-3-enylbenzene Chemical class C=1C=CC=CC=1C(C=1C=CC=CC=1)(CC=C)C1=CC=CC=C1 HFHRSBKYURPWRU-UHFFFAOYSA-N 0.000 description 1
- VFFBJZCCXOYRNN-UHFFFAOYSA-N 1-[4-[2-(dimethylamino)ethoxy]phenyl]-1,2-diphenylbutan-1-ol Chemical compound C=1C=CC=CC=1C(O)(C=1C=CC(OCCN(C)C)=CC=1)C(CC)C1=CC=CC=C1 VFFBJZCCXOYRNN-UHFFFAOYSA-N 0.000 description 1
- WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical group C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 1
- 125000003635 2-dimethylaminoethoxy group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 description 1
- CONKBQPVFMXDOV-QHCPKHFHSA-N 6-[(5S)-5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-2-oxo-1,3-oxazolidin-3-yl]-3H-1,3-benzoxazol-2-one Chemical group C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C[C@H]1CN(C(O1)=O)C1=CC2=C(NC(O2)=O)C=C1 CONKBQPVFMXDOV-QHCPKHFHSA-N 0.000 description 1
- 239000002028 Biomass Substances 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 101000927799 Homo sapiens Rho guanine nucleotide exchange factor 6 Proteins 0.000 description 1
- 102100033202 Rho guanine nucleotide exchange factor 6 Human genes 0.000 description 1
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- 238000010575 fractional recrystallization Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- FQZYTYWMLGAPFJ-OQKDUQJOSA-N tamoxifen citrate Chemical compound [H+].[H+].[H+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 FQZYTYWMLGAPFJ-OQKDUQJOSA-N 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (AREA)
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野コ
この発明は、トランス−１，１，２−トリフェニル−ブ
ドーｌ−エン誘導体の製造法に関するものである。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] This invention relates to a method for producing trans-1,1,2-triphenyl-budol-ene derivatives.
「従来の技術」
近年、抗エストロゲン特性をもつためホルモン依存性乳
房腫瘍の処置に適当な一連のトリフェニルブテン誘導体
が報告されてきた（Ｒ，スザーランドおよびＶ、Ｃ，ジ
ヨルダン［非ステロイド抗エストロゲン（Ｎｏｎｓｔｅ
ｒｏｉｄａｌ Ａｎｔｉｏｅｓｔｒｏｇｅｎｓ）Ｊア
カデミツク・プレス１９８１年）。PRIOR ART In recent years, a series of triphenylbutene derivatives have been reported that have anti-estrogenic properties and are therefore suitable for the treatment of hormone-dependent breast tumors (R, Sutherland and V, C, Dijordan [Non-steroidal anti-estrogens]). Nonste
(Roidal Antioestrogens) J Academic Press 1981).
活性成分ｌ−［４°−（２−ジメチルアミノエトキン）
フェニルコートランス−１，２−：、’フェニルブドー
ｌ−エンは、治療に用いられ、同時にタモキンフェン（
ＴＡＭＯＸ Ｉ ＰＥＮＸＩＮＮ）という名称で世界的
に知られるようになった。Active ingredient l-[4°-(2-dimethylaminoethquine)
Phenylcotrans-1,2-:'phenylbutol-ene is used for treatment and at the same time tamoquinfen (
It became known worldwide under the name TAMOX I PENXINN).
１．１．２−トリフェニル−ブドーｌ−エン誘導体の合
成時において、一般式２のノアステレオマ−性力ルビノ
ールの脱水段階で一般式３およびｌの幾何学的異性体オ
レフィン［シス／トランスまたはＥ／Ｚ体］が混合物中
に蓄積する。1.1.During the synthesis of 2-triphenyl-budol-l-ene derivatives, the dehydration step of the noastereomeric rubinol of general formula 2 is performed to remove the geometrically isomeric olefins of general formula 3 and l [cis/trans or E /Z-form] accumulates in the mixture.
Ｒｌｆｉ−ＩＪ３．−ＣＭ２ＣＭ、 、 Ｒ２ｍ −
Ｍ 、 ＯＫ 。Rlfi-IJ3. -CM2CM, , R2m -
M, OK.
活性異性体の１つだけが臨床適応されるため、生成する
異性体混合物から純トランス体を単離する必要があった
。これは、例えば分別再結晶化またはクロマトグラフィ
ーのような大きな損失と費用のかかる方法によってしか
いままでなされていなかった。［イギリス国特許番号１
０１３９０７号；アメリカ特許番号４，５３６，５１６
号；ヨーロッパ特許番号００５４１６８号；ｃ、Ｒ，ベ
ツドフォードおよびり、Ｎ リチャードソン、ネイチ
ャー（Ｎａｔｕｒｅ）、２１２巻、７３１７３４頁（１
９６６年）；Ｐ、ソバ゛−ら、アクタ・ヂミカ・アカデ
ミ力・サイエンスチカ・ハンガリア（Ａｃｔａ Ｃｈ
ｉｍＡｃａｄ、 Ｓｃｉ、 Ｈｕｎｇ、 ）、１００巻
６１−７４頁（１９７９年）：Ｄ、Ｗ、ロバートソンお
よびＪ、Ａカツエンエレンボーゲン、ジャーナル・オブ
・オーガニック・ケミストリー（Ｊ 、Ｑｒｇ、 Ｃｈ
ｅｍ、 ）、４７巻、２３８７−２３９３頁（１９８２
年）；ＰＣ，ルエニソツら、ジャーナル・オブ・メディ
シナル・ケミストリー（Ｊ 、 Ｍｅｄ、 Ｃｈｅｍ、
）、２５巻、１０５６−１０６０頁、Ｒ，Ｄ、アームス
トロング、ジャーナル・オブ・クロマトグラフィー（Ｊ
、 Ｃｈｒｏｍａｔｏｇｒ、 ）、４１４巻１９２−１
９６頁（１９８７年）］。Since only one of the active isomers is clinically indicated, it was necessary to isolate the pure trans isomer from the resulting isomer mixture. This has hitherto only been accomplished by costly and expensive methods, such as fractional recrystallization or chromatography. [British patent number 1
No. 013907; U.S. Patent No. 4,536,516
No.: European Patent No. 0054168; C, R, Bedford and Tori, N Richardson, Nature, vol. 212, p. 731,734 (1)
966); P.
imAcad, Sci, Hung, ), vol. 100, pp. 61-74 (1979): D. W. Robertson and J. A.
), vol. 47, pp. 2387-2393 (1982
); PC, Ruenisotz et al., Journal of Medicinal Chemistry (J, Med, Chem,
), vol. 25, pp. 1056-1060, Armstrong, R.D., Journal of Chromatography (J
, Chromatogr, ), Volume 414, 192-1
96 pages (1987)].
シス体が優勢な従来無価値の母液分画トランス体に変換
することが可能になってはじめてタモキシフェンの収率
を増加させることができる。ヨーロッパ特許番号０１２
７１”２８号に見られるように、シス体は上昇した温度
で強塩酸条件下でトランス体に変換することができる。The yield of tamoxifen can only be increased if it becomes possible to convert the conventionally worthless mother liquor fraction, in which the cis isomer is predominant, into the trans isomer. European patent number 012
As seen in No. 71''28, the cis form can be converted to the trans form under strong hydrochloric acid conditions at elevated temperatures.
驚くべきことに、一般式ｌのトランス−１，１゜２−ト
リフェニル−ブドー１−エン誘導体の製造方法における
実質的な単純化が可能になった。後に示すとおり、一般
式２を有するカルビノール化合物は、一定条件下で一般
式ｌを有するトランスオレフィンに１工程で大部分変換
される。それによって従来の製造方法で必要であった工
程、ａ）ノアステレオマ−性力ルビノールの脱水後のシ
ス／トランス異性体混合物の単離、
ｂ）結晶化またはクロマトグラフィーによるトランス体
の分離および
Ｃ）シス体が多い母液分画の再異性化
が省略することができる。Surprisingly, a substantial simplification in the process for the preparation of trans-1,1°2-triphenyl-budo-1-ene derivatives of the general formula l has become possible. As shown below, carbinol compounds having general formula 2 are largely converted in one step to transolefins having general formula 1 under certain conditions. Thereby the steps required in conventional production methods: a) isolation of the cis/trans isomer mixture after dehydration of the noastereomeric rubinol; b) separation of the trans isomer by crystallization or chromatography; and C) cis Re-isomerization of the mother liquor fraction, which is rich in biomass, can be omitted.
本発明による方法では、一般式２のカルビノールは有機
溶媒の不存在下で、上昇した温度で塩酸または硫酸の影
響下に一般式１のトランス−オレフィンに直接変換する
。これらの条件下で一般式３のシス−オレフィンの生成
は実質的に抑制される。In the process according to the invention, carbinols of the general formula 2 are converted directly into trans-olefins of the general formula 1 under the influence of hydrochloric acid or sulfuric acid at elevated temperatures in the absence of organic solvents. Under these conditions, the formation of cis-olefins of general formula 3 is substantially suppressed.
一般式２によるカルビノールの一般式１のトランス−オ
レフィンへの変換は、好ましくは５０６０℃の温度範囲
で実施される。塩酸または硫酸は上昇した温度で好まし
くは１２−１６時間、少なくとも１０時間作用させる。The conversion of carbinols according to general formula 2 into trans-olefins of general formula 1 is preferably carried out in the temperature range of 5060<0>C. The hydrochloric acid or sulfuric acid is allowed to act at elevated temperature, preferably for 12-16 hours, but at least 10 hours.
本発明を以下に述べる具体的な実施例に基づいてさらに
詳しく説明する。The present invention will be explained in more detail based on specific examples described below.
実施例１
１−［４’−（２−ジメチルアミノエトキシ）フェニル
］−１，２−ジフェニル−ブタン−１−オールの１部を
５０容慣％硫酸ＩＯ部中で撹拌し、懸副液を激しく撹拌
しながら１４時間５５℃に加熱する。続いて冷却し２．
５部の水と濃アンモニア１２．５部を加えアルカリ化し
−た。反応生成物を酢酸エチルで抽出し、有機層を水で
繰り返し洗浄した。真空下で有機溶媒を除去した後、ｌ
−［４゜（２−ジメチルアミノエトキシ）フェニル］−
トランスー！、２−ジフェニル−ブドーｌ−エン９４％
［ＨＰＬＣ］の０．９部の残渣が得られた。アセトンか
らの結晶は融点９８℃である。含量＝９９゜４％［ＨＰ
ＬＣ］。Example 1 One part of 1-[4'-(2-dimethylaminoethoxy)phenyl]-1,2-diphenyl-butan-1-ol was stirred in IO parts of 50% by volume sulfuric acid, and the suspended liquid was Heat to 55° C. for 14 hours with vigorous stirring. Next, cool 2.
5 parts of water and 12.5 parts of concentrated ammonia were added to make it alkaline. The reaction product was extracted with ethyl acetate, and the organic layer was washed repeatedly with water. After removing the organic solvent under vacuum, l
-[4゜(2-dimethylaminoethoxy)phenyl]-
Trance! , 2-diphenyl-budol-l-ene 94%
A residue of 0.9 parts of [HPLC] was obtained. Crystals from acetone have a melting point of 98°C. Content = 99°4% [HP
LC].
実施例２
１−［４°−（２−ジメチルアミノエトキシ）フェニル
］−１，２−ジフェニル−ブタン−１−オールの１部を
３２重量％の塩酸６部中で撹拌し、懸濁液を激しく撹拌
しながら１６時間５２℃に加熱する。続いて冷却し２部
の氷と濃アンモニア６部を加えアルカリ化した。反応生
成物を酢酸エチルで抽出し、有機層を水で繰り返し洗浄
した。真空下で有機溶媒を除去した後、ｌ−［４°−（
２−ジメチルアミノエトキシ）フェニルコートランス−
１゜２−ジフェニル−ブドー１−モン９６％［ＨＰＬＣ
］の０．９７部の残渣か得られた。メタノール／水から
の結晶は融点９６から９８℃である。含量：９９．７％
［ＨＰＬＣ］。Example 2 One part of 1-[4°-(2-dimethylaminoethoxy)phenyl]-1,2-diphenyl-butan-1-ol was stirred in 6 parts of 32% by weight hydrochloric acid and the suspension was Heat to 52°C for 16 hours with vigorous stirring. Subsequently, the mixture was cooled and alkalized by adding 2 parts of ice and 6 parts of concentrated ammonia. The reaction product was extracted with ethyl acetate, and the organic layer was washed repeatedly with water. After removing the organic solvent under vacuum, l-[4°-(
2-dimethylaminoethoxy)phenylcotrans-
1゜2-diphenyl-budo-1-mon 96% [HPLC
A residue of 0.97 parts was obtained. Crystals from methanol/water have a melting point of 96-98°C. Content: 99.7%
[HPLC].
実施例３
１−［４’−（２−ツメチルアミノエトキシ）フェニル
］−１−（３’−ヒドロキシフェニル）−２−フェニル
−ブタン−１−オールの１部を５０容量％の硫酸９部中
で撹拌し、懸濁液を激しく撹拌しながら１５時間５２℃
に加熱する。続いて冷却し３部の氷と濃アンモニア１２
部を加えアルカリ化した。Example 3 One part of 1-[4'-(2-trimethylaminoethoxy)phenyl]-1-(3'-hydroxyphenyl)-2-phenyl-butan-1-ol was added to 9 parts of 50% by volume sulfuric acid. and stirred the suspension at 52°C for 15 hours with vigorous stirring.
Heat to. Then cool and add 3 parts of ice and 12 parts of concentrated ammonia.
of the mixture was added to make it alkalized.
反応生成物をジクロロメタンで抽出し、有機層を水で繰
り返し洗浄した。真空下で有機溶媒を除去した後、１−
［４°−（２−ジメチルアミノエトキシ）フェニルコー
トランス−１−（３°−ヒドロキシフェニル）−２−フ
ェニル−ブドーミーエン９０％［ＨＰＬＣ］の０．９部
の残渣が得られた。エタノールからの結晶は融点１６４
℃である。含ｍ：９９．５％［ＨＰＬＣ］。The reaction product was extracted with dichloromethane and the organic layer was washed repeatedly with water. After removing the organic solvent under vacuum, 1-
A residue of 0.9 parts of [4°-(2-dimethylaminoethoxy)phenylcotrans-1-(3°-hydroxyphenyl)-2-phenyl-budomiene 90% [HPLC] was obtained. Crystals from ethanol have a melting point of 164
It is ℃. Contains m: 99.5% [HPLC].
実施例４
１−［４°−（２−ジメチルアミノエトキシ）フェニル
］−１−（３’−ヒドロキシフェニル）−２−フェニル
−ブタン−１−オールの１部を３７重量％の塩酸６部中
で撹拌し、懸濁液を激しく撹拌しながら１６時間５０℃
に加熱する。続いて冷却し３部の水と濃アンモニア４部
を加えアルカリ化した。Example 4 1 part of 1-[4°-(2-dimethylaminoethoxy)phenyl]-1-(3'-hydroxyphenyl)-2-phenyl-butan-1-ol in 6 parts of 37% by weight hydrochloric acid The suspension was heated at 50°C for 16 hours with vigorous stirring.
Heat to. Subsequently, the mixture was cooled and alkalized by adding 3 parts of water and 4 parts of concentrated ammonia.
反応生成物をジクロロメタンで抽出し、有機層を水で繰
り返し洗浄した。真空下で有機溶媒を除去した後、１−
［４’−（２−ツメチルアミノエトキシ）フェニルコー
トランス−１−（３°−ヒドロキシフェニル）−２−フ
ェニル−ブドーｌ−エン９３％［ＨＰＬＣ］の０．８５
部の残渣が得られた。エタノールからの結晶は融点１６
４℃である。含量：９９．６％［ＨＰＬＣ］。The reaction product was extracted with dichloromethane and the organic layer was washed repeatedly with water. After removing the organic solvent under vacuum, 1-
0.85 of [4'-(2-trimethylaminoethoxy)phenylcotrans-1-(3°-hydroxyphenyl)-2-phenyl-budol-l-ene 93% [HPLC]
A residue of 50% was obtained. Crystals from ethanol have a melting point of 16
It is 4℃. Content: 99.6% [HPLC].
、実施例５
１−［４°−（２−ジエチルアミノエトキシ）フェニル
］−１−（３°−ヒドロキシフェニル）−２−フェニル
−ブタン−１−オールの１部を３７重量％の塩酸８部中
で撹拌し、懸濁液を激しく撹拌しながら１５時間５２℃
に加熱する。続いて冷却し４部の氷と濃アンモニア５部
を加えアルカリ化した。, Example 5 1 part of 1-[4°-(2-diethylaminoethoxy)phenyl]-1-(3°-hydroxyphenyl)-2-phenyl-butan-1-ol in 8 parts of 37% by weight hydrochloric acid The suspension was heated at 52°C for 15 hours with vigorous stirring.
Heat to. Subsequently, the mixture was cooled and alkalized by adding 4 parts of ice and 5 parts of concentrated ammonia.
反応生成物をジクロロメタンで抽出し、有機層を水で繰
り返し洗浄した。真空下で有機溶媒を除去した後、１−
［４°−（２−ジエチルアミノエトキシ）フェニルコー
トランス−１−（３°−ヒドロキシフェニル）−２−フ
ェニル−ブドーｌ−エン９５％［ＨＰＬＣ］の０．９５
部の残渣が得られた。イソプロパツールからの結晶は融
点１３０℃である。The reaction product was extracted with dichloromethane and the organic layer was washed repeatedly with water. After removing the organic solvent under vacuum, 1-
0.95 of [4°-(2-diethylaminoethoxy)phenylcotrans-1-(3°-hydroxyphenyl)-2-phenyl-budol-l-ene 95% [HPLC]
A residue of 50% was obtained. Crystals from isopropanol have a melting point of 130°C.
含量：９９．５％［ＨＰＬＣ］。Content: 99.5% [HPLC].
Claims (2)
である］ 強塩酸または硫酸性の有機溶媒を除外した媒質中で加熱
し、反応生成物を常法で処理することからなる、 一般式、▲数式、化学式、表等があります▼ ［式中、Ｒ＾１はＣＨ＿３、ＣＨ＿２ＣＨ＿３およびＲ
＾２はＨ、ＯＨである、］ を有するトランス−１，１，２−トリフェニル−ブト−
１−エン誘導体の製造方法。(1) General formula, ▲Mathematical formula, chemical formula, table, etc.▼ [In the formula, R^1 and R^2 have the meanings defined in General formula 1] Medium excluding strong hydrochloric acid or sulfuric acid organic solvents There are general formulas, ▲mathematical formulas, chemical formulas, tables, etc., which consist of heating in a reactor and treating the reaction products in a conventional manner.[In the formula, R^1 is CH_3, CH_2CH_3 and R
^2 is H, OH, trans-1,1,2-triphenyl-but-
Method for producing a 1-ene derivative.
から３７重量％で、硫酸濃度が少なくとも４０容量％好
ましくは４５から５０容量％の範囲内である請求項１記
載の方法。(2) Hydrochloric acid concentration is at least 25% by weight, preferably 32%
37% by weight and the sulfuric acid concentration is at least 40% by volume, preferably in the range from 45 to 50% by volume.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63332691A JPH0739379B2 (en) | 1988-12-28 | 1988-12-28 | Process for producing trans-1,1,2-triphenyl-but-1-ene derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63332691A JPH0739379B2 (en) | 1988-12-28 | 1988-12-28 | Process for producing trans-1,1,2-triphenyl-but-1-ene derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02184659A true JPH02184659A (en) | 1990-07-19 |
| JPH0739379B2 JPH0739379B2 (en) | 1995-05-01 |
Family
ID=18257803
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63332691A Expired - Lifetime JPH0739379B2 (en) | 1988-12-28 | 1988-12-28 | Process for producing trans-1,1,2-triphenyl-but-1-ene derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0739379B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006241101A (en) * | 2005-03-04 | 2006-09-14 | Tokyo Univ Of Science | Method for producing droloxifene |
| JP2008074711A (en) * | 2006-09-19 | 2008-04-03 | Okayama Univ | Method for producing triarylethylethene derivative |
| JP2021521163A (en) * | 2018-04-09 | 2021-08-26 | 上海科技大学Ｓｈａｎｇｈａｉ Ｔｅｃｈ Ｕｎｉｖｅｒｓｉｔｙ | Target proteolytic compounds, their antitumor applications, their intermediates and their applications |
-
1988
- 1988-12-28 JP JP63332691A patent/JPH0739379B2/en not_active Expired - Lifetime
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006241101A (en) * | 2005-03-04 | 2006-09-14 | Tokyo Univ Of Science | Method for producing droloxifene |
| JP4572407B2 (en) * | 2005-03-04 | 2010-11-04 | 学校法人東京理科大学 | Method for producing droloxifene |
| JP2008074711A (en) * | 2006-09-19 | 2008-04-03 | Okayama Univ | Method for producing triarylethylethene derivative |
| JP2021521163A (en) * | 2018-04-09 | 2021-08-26 | 上海科技大学Ｓｈａｎｇｈａｉ Ｔｅｃｈ Ｕｎｉｖｅｒｓｉｔｙ | Target proteolytic compounds, their antitumor applications, their intermediates and their applications |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0739379B2 (en) | 1995-05-01 |
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